NM_001164310.3:c.292G>T

Variant names:

• chr9-35563075-C-A
• rs761538272
• NM_001164310.3:c.292G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001164310.3(CIMIP2B):​c.292G>T​(p.Val98Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V98I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CIMIP2B NM_001164310.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.465
• Publications: 0 publications found

Genes affected

CIMIP2B (HGNC:34242): (ciliary microtubule inner protein 2B)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29914773).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164310.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIMIP2B	NM_001164310.3	MANE Select	c.292G>T	p.Val98Leu	missense	Exon 3 of 6	NP_001157782.1	A8MTA8-1
	CIMIP2B	NM_001287239.2		c.292G>T	p.Val98Leu	missense	Exon 3 of 6	NP_001274168.1
	CIMIP2B	NM_001287238.2		c.292G>T	p.Val98Leu	missense	Exon 3 of 6	NP_001274167.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIMIP2B	ENST00000399742.7	TSL:1 MANE Select	c.292G>T	p.Val98Leu	missense	Exon 3 of 6	ENSP00000382646.2	A8MTA8-1
	CIMIP2B	ENST00000447837.1	TSL:1	c.292G>T	p.Val98Leu	missense	Exon 3 of 6	ENSP00000412746.1	A8MTA8-2
	CIMIP2B	ENST00000492890.5	TSL:5	c.259G>T	p.Val87Leu	missense	Exon 3 of 6	ENSP00000513459.1	A0A8V8TLC2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248948 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461614 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727066

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111790

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.47
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Benign	0.036	D
Sift4G	Uncertain	0.036	D
Polyphen		0.43	B
Vest4		0.45
MutPred		0.39		Gain of loop (P = 0.1069)
MVP		0.067
MPC		0.085
ClinPred		0.30	T
GERP RS		0.35
Varity_R		0.11
gMVP		0.48
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs761538272; hg19: chr9-35563072;